New evidence from several sources suggests that therapeutic responses to monoamine oxidase-inhibiting antidepressants occur in conjunction with reduced sympathetic outflow from the central nervous system. These noradrenergic neurotransmitter system changes develop only after longer-term drug administration. Depressed patients as a group have some corresponding evidence of enhanced sympathetic activity, including elevated plasma norepinephrine levels and, in a smaller subgroup of patients, and insensitivity to post-synaptic adrenergic agonists. At the same time, differences in cortisol responses to clonidine in depressed patients compared to normals indicated that normalization of elevated plasma cortisol concentrations present in some depressed patients can be achieved by clonidine, an Alpha2-noradrenergic agonist which does not reduce cortisol in normals--raising the question of a link between cortisol hypersecretion and noradrenergic dysfunction in depression. Other studies completd this year have examined additional elements in noradrenergic and seotonergic receptor function and neuroendocrine responsivity in depression, and have begun to evaluate possible common biological factors and treatment responses which might be present in patients with other diagnoses besides primary affective disorders.